The broad and long-term goals of this proposal are to form a significant knowledge-base surrounding the role aged astrocytes in the propogation of neurodegenerative sequelae after TBI. TBI in the aged population represents a significant unmet healthcare challenge, as advanced aging is the greatest risk factor for acquiring a TBI, and subsequently developing neurodegenerative disease such as dementia, Alzheimer?s- and Parkinson?s disease. Cumulatively, the research design takes advantage of specific inflammatory hallmarks and functional modulators associated with dystrophic astrocytes, in an attempt to delineate their respective contributions to neuronal pathology and cognitive dysfunction. Ultimately, we will determine if harnessing astrocytes via novel AAV constructs in aged TBI models is associated with improving neuronal and cognitive outcome measures.